Aim of the study
3β-Hydroxysteroid dehydrogenase (3β-HSD1) catalyses the production of steroid precursors for androgens and estrogens, which play an essential role in cancer metastasis. We explored the potency and mode of action of curcuminoids and their metabolites of inhibiting 3β-HSD1 activity and compared the species difference between human and rat. Materials and
Conclusion
Some curcuminoids are potent human placental 3β-HSD1 inhibitors, possibly being potential drugs to treat prostate cancer and breast cancer.
Methods
In this study, we investigated the direct inhibition of 6 curcuminoids on human placental 3β-HSD1 activity and compared the species-dependent difference in human 3β-HSD1 and rat placental homolog 3β-HSD4.
Results
The inhibitory potency of curcuminoids on human 3β-HSD1 was demethoxycurcumin (IC50, 0.18 μM) > bisdemethoxycurcumin (0.21 μM)>curcumin (2.41 μM)> dihydrocurcumin (4.13 μM)>tetrahydrocurcumin (15.78 μM)>octahydrocurcumin (ineffective at 100 μM). The inhibitory potency of curcuminoids on rat 3β-HSD4 was bisdemethoxycurcumin (3.34 μM)>dihydrocurcumin (5.12 μM)>tetrahydrocurcumin (41.82 μM)>demethoxycurcumin (88.10 μM)>curcumin (137.06 μM)> octahydrocurcumin (ineffective at 100 μM). Human choriocarcinoma JAr cells with curcuminoid treatment showed that these chemicals had similar potency to inhibit progesterone secretion under basal and 8bromo-cAMP stimulated conditions. Docking analysis showed that all chemicals bind pregnenolone-binding site with mixed/competitive mode for 3β-HSD.